Focal cerebral ischemia in the rat produces rapid changes in gene expression (pattern of de novo protein synthesis) that include elements of the eukaryotic "stress response": 1) most proteins fail to be synthesized, 2) 5-9 proteins undergo preferential synthesis with different blood flow thresholds for their individual induction. What role these changes play in the pathogenesis of ischemic damage is not known. The principle objective is to identify which, if any, of the 5-9 proteins are consistently associated with 1) complete recovery, and 2) with irreversible injury. The second major objective is to determine whether these proteins are mechanistically important in the death or survival of brain cells: Are individual proteins early markers of cell death? of sustained metabolic trauma? of successful cellular repair? Do either of the Mr 27,000 and Mr 70,000 "stress proteins" confer tissue resistance to further ischemic stress? Focal, graded cortical ischemia in the rat will be achieved by occluding the middle cerebral and common carotid arteries. At 3 hr, 6 hr or 24 hr of ischemia, cortical proteins will be pulse-labeled with intracerebral injections of a (3H)amino acid mixture and examined by two-dimensional gel fluorography. Blood flow will be quantified with a (14C)iodoantipyrine technique, and (in 24 hr animals) infarct volume will be measured to permit direct correlations between patterns of protein synthesis, blood flow and cortical tissue damage. Inhibitors of protein synthesis, physiologic manipulations that favorably or adversely affect ischemic injury will be added to this paradigm to further characterize the relationship between the 5-9 proteins and tissue viability.